title: Biological activity of bis-benzimidazole derivatives on DNA topoisomerase I and HeLa, MCF7 and A431 cells.
abstract: Benzimidazoles of both natural and synthetic sources are the key components of many bio-active compounds. Several reports have shown antifungal, antiviral, H(2) receptor blocker and antitumor activities for benzimidazoles and their derivatives. In this study, we synthesized twelve bis-benzimidazole derivatives by selecting di(1H-benzo[d]imidazol-2-yl)methane as the main compound. The numbers of carbons at 2 positions of bis-benzimidazole derivatives were changed from 1 to 4, and derivatives were synthesized with methyl substitutions at 5- and/or 6- positions. The compounds were screened via in vitro plasmid superciol relaxation assays using mammalian DNA topoisomerase I and cytostatic assays were carried out against HeLa (cervix adenocarcinoma), MCF7 (breast adenocarcinoma) and A431 (skin epidermoid carcinoma) cells for selected derivatives. Our results suggest that the malonic acid derivatives of bis-benzimidazoles, namely, bis(5-methyl-1H-benzo[d]imidazol-2-yl)methane and bis(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)methane, were remarkably active compounds in interfering with DNA topoisomerase I and the former compound was also found to be cytotoxic against MCF7 and A431 cells. The inhibitory effects obtained with these derivatives are significant as these compounds can be potential sources of anticancer agents.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, Izmir, 35100, Turkey.
authors.forename: A Selcen
authors.initials: AS
authors.lastname: Alpan
authors.forename: Sevil
authors.initials: S
authors.lastname: Zencir
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.forename: Gunes
authors.initials: G
authors.lastname: Coban
authors.forename: Borbála
authors.initials: B
authors.lastname: Réthy
authors.forename: H Semih
authors.initials: HS
authors.lastname: Gunes
authors.forename: Zeki
authors.initials: Z
authors.lastname: Topcu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D002583:Uterine Cervical Neoplasms / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D059004:Topoisomerase I Inhibitors; C009712:bis-benzimidazole; D004264:DNA Topoisomerases, Type I